The overall goal of this project is to gain a better understanding of the mechanisms which regulate cell proliferation and tissue growth in the eye, particularly retinal vessels and the ocular lens, and the manner in which these and other tissues of the eye interact. (e.g. the mechanism of which puncture of the lens capsule in the rat leads to stimulation of the cell cycle in rat retinal venular endothelium). It is hoped to help clarify the nature of the control of capillary and vessel growth during normal development and following injuries which lead to neovascularization and possible blindness. The specific aims are to study changes in ocular vascular endothelium associated with the initiation of cell division and to continue our studies along related lines on wound healing in the lens epithelium and lens fiber regeneration. In order to characterize the early events in vascular endothelium following injury (Deem, Futterman, Kalina model), ultrastructural changes and changes in the surface membranes (particularly those occurring prior to the onset of DNA synthesis) will be sought using both T.E.M. and S.E.M. The vascular endothelial lining will also be studied with regard to changes in permeability to enzyme markrers (peroxidase and myoglobin) which can be localized cytochemically at the E.M. level. Changes in macromolecular synthesis (RNA, Protein; using labeled precursors and autoradiography of retinal digest preparations) will be sought as well as the activation of ribosomal production, both of these being characteristic of the G-O yields G-1 transition in other cells. Possible mitogenic agents acting on vascular endothelium and a comparison with the known mitogenic agents for the lens (insulin, serum fractions etc.) will be sought. The possible existence of subphases during the pre-DNA synthetic period, such as those that exist in the lens, will also be investigated. The subsequent growth of new vessels will be studied with the S.E.M. of plastic corrosion casts. Tissue culture of renal vasculature is also planned in order to study the distribution of H3-thymidine incorporating cells at different times after explantation, and the effects of potential mitogenic factors.